Motivation and emotion/Book/2017/Ghrelin, leptin, hunger, and eating
How do ghrelin and leptin affect hunger and eating?
Overview[edit | edit source]
Have you ever wondered why we feel hungry or full? Perhaps you have considered how the feeling of hunger and satiety transpire and what biological process the human body undergoes to feel these sensations? Maybe you have even contemplated how hunger can motivate us to eat?
These are the questions this chapter will strive to answer by exploring how ghrelin and leptin affect hunger and eating. It will explore how biological systems involving the hormones ghrelin and leptin work in conjunction with neural brain circuits and bodily organs to direct the body's attentions and actions towards seeking out food. To explain how this occurs within the body, and how this physiological need is met, the Dual-Control theory, the Glucostatic theory, Lipostatic theory and the Set-Point theory of hunger regulation will be examined.
After reading this chapter, the following learning outcomes will have been addressed:
Hunger[edit | edit source]
Hunger in humans, as in other organisms, is a physiological need involving biological systems such as neural brain circuits, hormones, and organ systems (Saper et al., 2002). Eating behaviour can be separated into hedonic feeding and homeostatic feeding. This chapter acknowledges that eating can occur without hunger in response to emotional and social factors, and can extend beyond satiety (Saper et al., 2002). However, the focus of this chapter is on homeostatic feeding and how hormones in the body produce hunger and satiety.
According to Maslow's hierarchy of needs, needs can be categorised as growth needs and deficiency needs. In the case of physiological needs, such as hunger, they are categorised as deficiency needs. In deficiency needs, everything is fine physiologically until some sort of deficiency activates a need within an organism to interact with the environment to correct the deficit. Hence, when a physiological need is unmet for some time it generates a motivational state that dominates consciousness (Maslow, 1943).
Case study[edit | edit source]
The case study below will be used throughout the chapter to exemplify how ghrelin and leptin work in conjunction with biological systems and neural brain circuits to motivate eating behaviour. It will also cover how psychological theories relate to eating and hunger.
Follow Homer's story. It will provide an example to help you understand how ghrelin and leptin motivate hunger and eating.
Hunger as a motivational state[edit | edit source]
When a person has been deprived of food for several hours, blood plasma levels of glucose drop (Saper et al., 2002). The deficit in blood glucose activates other biological systems which involve rising levels of the hunger-inducing hormone ghrelin (Saper et al., 2002). Also involved are digestive organs and neural brain circuits within the body. Together the deficit and biological systems create the motivational state of hunger. Initially, a state of hunger can be ignored and overridden when attending to more important tasks, but eventually the need will become so great that it dominates consciousness (Maslow, 1943; Saper et al., 2002). Seeking out food and eating becomes the focus of a persons' thoughts and behaviours as this will rid the feeling of hunger. In this way, the body has successfully been able to bring itself back to a state of homeostasis (Broberger, 2005), (Saper et al., 2002).
Eating restores blood glucose levels, corrects the deficit, alleviates the motivational state and returns the body to a state of homeostasis. Once the hunger has been satiated, with the help of leptin, the salience of hunger fades and the need is forgotten for a while. That is, until blood glucose levels drop, hunger hits and the cycle begins again (Maslow, 1943), (Saper et al., 2002).
Satiety is an important part of homeostatic feeding, it can be seen as a negative feedback system for hunger and a motivational state to stop eating (Malik et al., 2008). One of the main hormones that contributes to satiety is leptin. During eating, the levels of ghrelin fall while the levels of leptin rise (Saper et al., 2002).
It's nearing lunch time and Homer has been working in section 7G all morning. He has been feeling peckish most of this time. Suddenly, Homer feels so hungry that all he can think about is taking a break so he can eat lunch. His hunger is motivating his thoughts and actions towards seeking out and eating food.
Keep following for a more thorough discussion on how the hormones ghrelin and leptin relate to this motivation
Hormones[edit | edit source]
Hormones play a major role in homeostatic feeding. The two main hormones associated with hunger and satiety are ghrelin and leptin. Other peptide hormones are involved with the process, these include Insulin, neuropeptide Y , Agouti-related protein (AgRP) and cholecystokinin (CCK) (Broberger, 2005).
Ghrelin[edit | edit source]
Ghrelin, also known as "the hunger hormone", was first discovered in 1999 and is a gastrointestinal neuropeptide produced and released by epsilon cells in the fundus of the stomach (Hellstron, 2009). Small amounts of ghrelin are also produced and released by the hypothalamus, pancreas and small intestine (Hellstron, 2009). It was discovered by Kojima et al., (1999) that ghrelin levels increase during food deprivation and peak preprandially. It was also found that ghrelin decreased back to baseline levels within an hour postprandially (Kojima et al., 1999). This demonstrates that rising ghrelin levels function as an important signal to induce hunger (Kojima et al.,1999). In 2000, ghrelin was discovered to control systemic metabolism via the activation of orexigenic neural circuits (Müller et al., 2015).
The main site of action for ghrelin on feeding regulation is the hypothalamus, where ghrelin receptors are found in the arcuate nuclei (ARC) and the ventromedial hypothalamus (VMH) (Müller et al., 2015). In addition, Agouti-related protein (AgRP) receptors in the VMH have also been found to exhibit ghrelin receptors (Müller et. al, 2015).
One of the factors found to have an effect on ghrelin levels is sleep deprivation. In a study conducted by Broussard et al., (2016), one night of sleep deprivation was found to have a significant effect on elevating ghrelin levels in men of average weight. The observed elevated levels also correlated with higher calorie intake, especially at night. The authors conclude that elevated ghrelin levels may be a mechanism by which sleep loss leads to increased food intake and the development of obesity (Broussard et al., 2016).
Although ghrelin has been well established as "the hunger hormone" it has been found to have other functions. Hellstron (2009) stated that ghrelin has a motility effect in most parts of the gastrointestinal (GI) tract and also increases colonic emptying in mice. He also states that ghrelin exhibits an anti-inflammatory effect in the GI tract. In a study conducted by DeBoer (2011), it was found that ghrelin not only increased motility in the GI tract and had an anti-inflammatory effect, but it also increased colonic blood flow. Although more research in humans is needed, it has been suggested that ghrelin may be an effective treatment for inflammatory bowel diseases such as Crohn's disease and ulcerative colitis (DeBoer, 2011).
Leptin[edit | edit source]
Leptin was discovered in 1994 and is produced and secreted by the bodies adipose tissues. However, small amounts are also produced in other tissues such as the placenta, stomach, mammary epithelium and the heart (Klok et al., 2007).
Leptin is the main hormone which induces satiation or a feeling of fullness after a meal, therefore, when levels are high, hunger is decreased (Klok et al., 2007). Due to the effect that leptin has on the body, it can be seen as a negative feedback system for eating behaviour (Ahima & Flier, 2000). This feedback system occurs due to the gut-brain axis communicating with the brain once eating has been initiated. In response to this information, ghrelin levels begin to fall, as ghrelin levels fall, leptin levels rise (Berthoud et al., 2017), (Klok et al., 2007).
Leptin creates the feeling of satiety by binding to neurons in key regulatory centres in the hypothalamus to inhibit food intake (Ahima & Flier, 2000). The key regulatory centres in the hypothalamus that exhibit leptin receptors are expressed in the arcuate nuclei (ARC), and the ventromedial hypothalamus (VMH) much like ghrelin. However, receptors can also be found in the dorsomedial hypothalamic nucleus (DMH) (Shufen, 2016).
Leptin has a key role in energy homeostasis because it is able to alert the brain to the state of body adiposity (Ahima & Flier, 2000). Leptin levels in circulation are increased in proportion to fat mass. The more adipose tissue the body has, the more leptin is released (Gale et al., 2004). It is this information which enables the brain to work out much body fat exists (Klok, et al., 2007). Through this feedback system leptin is a mediator in long-term regulation of energy homeostasis. It has the ability to reduce food intake and thereby induce weight loss when body fat is too high (Klok, et al., 2007).
While leptin acts as the main satiety hormone in the body and plays a key role in energy homeostasis, it has also has other functions. Klok et al., (2007) reports that leptin influences various biological mechanisms, including immune and inflammatory responses, bone formation, wound healing, formation of blood cells (haematopoiesis) and formation of blood vessels (angiogenesis).
Homer is now eating lunch and beginning to feel full. One more bite and he's done. The main hormone that influenced Homer's decision to stop eating is leptin. This is because during eating, Homer's ghrelin decreased while his leptin increased. When leptin is high, hunger decreases.
Keep reading to find out how biological systems communicate with the brain to motivate eating behaviour.
Choose the correct answer and click "Submit":
Biological systems associated with hunger and satiety[edit | edit source]
Biological systems are involved in creating the motivational state of hunger; these systems are listed below.
Brain structures[edit | edit source]
The hypothalamus is involved in homeostatic feeding; it is a region in the brain which is linked to the nervous system and the endocrine system through the pituitary gland (Ahima & Antwi, 2008). It is roughly the size of an almond and is located superior to the brain stem. The hypothalamus is responsible for many biological functions apart from Hunger such as, blood pressure, body temperature, heart rate, thirst and sexual desire. Hence, the Hypothalamus is the main regulator of homeostasis (Ahima & Antwi, 2008).
In 1954, the Dual-Control theory of hunger, a homeostatic view of hunger and satiety, was put forward by Elliot Stellar. It postulated that the Ventromedial hypothalamus (VMH) and the Lateral hypothalamus (LH) were responsible for homeostatic feeding (Broberger, 2005). According to this theory, the LH is the hunger centre and the VMH is the satiety centre. A series of experiments were conducted which involved leisoning of brain structures in rats. Rats that had their LH lesioned exhibited severe weight loss through refusal to eat and drink. On the contrary, rats that had their VMH lesioned exhibited hyperphagia. This resulted in excessive eating, which lead to weight gain and obesity (Broberger, 2005).
[[|thumb| Figure 6. Diagram of the gut-brain axis (biological system). |270x270px]]
Gut brain axis[edit | edit source]
The gut-brain axis refers to the relationship between the gastrointestinal tract (GI) and the central nervous system (CNS). The gut-brain axis is a complex biochemical signalling system and involves not only the GI tract and the CNS but also the enteric nervous system which includes both the vagus nerve and the gut microbiota (Konturek, 2004). The gut-brain axis involves the neuroendocrine system, neuroimmune system and the hypothalamic-pituitary-adrenal axis (Konturek, 2004). It also includes both the sympathetic and parasympathetic components of the autonomic nervous system (Konturek, 2004). As the gut and brain are directly connected through this axis, signalling is bi-directional and therefore an upset gut can send distress signals to the brain and vice-versa (Konturek, 2004).
The gut-brain axis aids in satiety as it possesses mechanosensors and chemoreceptors, which it uses to sense the volume and nutrient content of consumed food (Berthoud et al., 2017). As the GI tract is densely innervated by vagal sensory nerves which are mentioned above, the GI tract can directly communicate nutritional information, as well as stomach stretch information from the gut to brain (Berthoud et al., 2017). According to Berthoud et al., (2017), gut microbes acting locally in the GI tract are also able to convey information to the brain to alter feeding behaviour through the gut brain axis.
In line with the Dual-Control theory, Homer's lateral hypothalamus received signals from his body to activate the feeling of hunger. This happened because:
Together, this generated the motivation for Homer to seek out and eat food. Once Homer started to eat his lunch:
Together, these hormones and biological systems, involving neural pathways, created the feeling of satiety and motivated Homer's decision to stop eating.
The role of ghrelin and leptin in obesity[edit | edit source]
Body weight and energy balance is regulated by a complex system. Two of the hormones that play a key role in the regulation of food intake and body weight are ghrelin and leptin. These hormones as already described, are produced and released by tissues and organs, and then signal through different pathways to the hypothalamus. In Obesity however, ghrelin and leptin systems and signalling pathways are disturbed.
In obese humans, circulating leptin levels are increased and circulating ghrelin levels are decreased (Broberger, 2005). In addition, Obese humans show limited effects to leptin treatment which, involves exogenous leptin administration (Shufen, 2015). This suggests that obese humans are leptin resistant.
Leptin resistance occurs in response to over exposure to sustained elevated leptin levels, due to over eating (Klock et al., 2007). This sustained exposure has a damaging effect on the hypothalamus that causes the hypothalamus to become less sensitive to leptin and therefore, leptin resistant (Klock et al., 2007). Because the hypothalamus is insensitive to leptin, a vicious cycle is created. The registering of satiety takes longer which therefore leads to more hunger, more over eating, more leptin production and more weight gain (Klock et al., 2007).
In addition to being leptin resistant, when obese humans do successfully lose weight, their levels of ghrelin become highly elevated, as if to compensate for the weight loss (Gale et al.,2004). It has been recommended that the development of a ghrelin antagonist or inhibitor, to control appetite, would be an important pharmaceutical development in the management of obesity to replace failed leptin therapy (Gale et al.,2004). Leptin resistance may also be treated with a low GI, high protein diet that includes natural fats (Shufen, 2016).
[edit | edit source]
There are a number of psychological theories associated with homeostatic hunger. The dual-control theory (a biological system theory) was mentioned earlier. Below you will find theories that centre around varying levels of glucose, ghrelin and leptin. You will also find links to short youtube videos to further your understanding of these theories.
Glucostatic model[edit | edit source]
In the 1950s Mayer put forward the Glucostatic theory, which is a short term initiating model of hunger. This theory postulated that low levels of blood plasma glucose initiated hunger while high concentration levels of blood plasma glucose concentration terminated hunger. In other words, Mayer postulated that hunger and satiety were both controlled by varying levels of blood plasma concentrations of Glucose (Mayer, 1955). Further, Mayer postulated that the rising levels of blood glucose concentrations during a meal were sensed by glucoreceptor neurons in the hypothalamus, which is what ultimately signalled meal termination (Mayer, 1955). The theory started losing popularity in the 1980s as researchers discovered that hunger and satiety involved a more complex process than what was proposed by Mayer (Chaput and Tremblay, 2009). One positive critcism with Mayers’ theory is that hunger does coincide with low levels of blood glucose, as this initiates a rise in ghrelin. Another positive critcism is that meal termination does coincide with higher levels of blood glucose, as this coincides with a drop in ghrelin and a rise in leptin. Mayers’ theory was found to be partly incorrect decades later due to Mayer missing the hormonal components of eating behaviour (hormones which were yet to be discovered at the time of his theory). However, the glucostatic theory is still relevant today, in 2009 Chaput and Tremblay found Mayers’ theory relevant in regards to their study on glucose instability, excess energy intake, high body mass and impaired glucose tolerance .
Lipostatic theory[edit | edit source]
The Lipostatic theory put forward by Kennedy postulated a short-term model of homeostatic hunger. The Lipostatic theory proposes that when stored fat drops below the bodies homeostatic balance adipose tissues secrete hormones into the bloodstream to increase food intake and promote weight gain (Gale et al., 2004). It also proposes when stored fat increases above the bodies homeostatic balance, adipose tissues release leptin into the bloodstream to promote weight loss and reduce food consumption (Gale et al., 2004).
Set-point theory[edit | edit source]
A long-term model of homeostatic hunger and energy homeostasis named the set-point theory was put forward by Gurin and Bennet. This theory proposes that the body has a genetically predetermined and preferred body weight. It further proposes that the body protects stored fat to remain at that predetermined weight by utilising the hormone leptin and body adiposity feedback (Berthoud et al., 2017).
Homer may be suffering from some degree of leptin insensitivity. At 239 pounds he is considered obese. In addition, Homer's family make comments that he sometimes eats much more than other people before feeling satiated.
Even though it's quite possible that Homer may be suffering from a degree of leptin resistance, it's not all doom and gloom. Homer may want to speak to his healthcare professional to reduce and reverse his leptin insensitivity. This can be achieved through a low GI, high protein diet that includes natural fats. In doing so his body will be better able to maintain an energy balance and a stable and healthy body fat percentage.
Conclusion[edit | edit source]
Hunger and eating are motivated by physiological deficits which are ameliorated by complex systems involving hormones. Biological systems such as the gut-brain axis and neural brain circuits can be thought of as conduits, through which the hormones ghrelin and leptin create the feeling of hunger and satiety.
Ghrelin and leptin create the feeling of hunger and satiety due to their fluctuating levels. When ghrelin is high and leptin is low, a feeling of hunger transpires. Once eating has been initiated, ghrelin levels fall and leptin levels rise. Due to the rise in leptin a feeling of satiety occurs. This occurrence is in line with Mayer’s Glucostatic theory. Which, explains how short term hunger occurs and how it motivates eating
Neural circuits involved in hunger and satiety are located in the hypothalamus, which is in line with the Dual-Control theory. This theory postulates that the LH is the feeding centre and the VMH is the satiety centre.
Ghrelin and leptin also play a role in obesity. When leptin levels are chronically elevated due to over-eating, damage to the hypothalamus can occur. This damage can make the hypothalamus less sensitive to leptin. This is problematic because this damage leads to leptin resistance and causes obesity.
When an obese person loses weight their ghrelin levels are increased as if to make up for the weight loss. This occurrence is in line with both the set point theory and the Lipostatic theory. The Lipostatic theory is a short-term model and the set-point theory is a long-term model. However, both postulate that the body will protect its fat stores and return them back to previous levels. It is in leptin deficiency that the problem with the Lipostatic and the set-point theory occur. As the hypothalamus isn’t registering leptin, due to leptin insensitivity, it believes that fat stores are critically low. Hence it fights to return the body back to an obese state.
Ghrelin and leptin contribute to eating and hunger through biological systems and neural circuits within the body and brain. It is the hunger and satiety created by these hormones, biological systems and neural circuits that create the motivation to eat and to stop eating.
See also[edit | edit source]
- Eating disorders and motivation (Book chapter, 2016)
- Hunger motivation (Book chapter, 2010)
- Hypothalamus and motivation (Book Chapter, 2017)
References[edit | edit source]
Ahima, R. S., & Flier, J. S. (2000). Leptin. Annual Review of Physiology, 62(1), 413-437. http://dx.doi.org/10.1146/annurev.physiol.62.1.413
Berthoud, H., Munzberg, H., & Morrison, C. D. (2017). Blaming the brain for obesity: Integration of hedonic and homeostatic mechanisms. Gastroenterology, 152(7) 1728-1738. http://dx.doi.org/10.1053/j.gastro.2016.12.050
Broberger, C. (2005). Brain regulation of food intake and appetite: Molecules and networks. Journal of Internal Medicine, 258(4), 301-327. http://dx.doi.org/10.1111/j.1365-2796.2005.01553.x
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Malik, S., McGlone, F., Bedrossian, D., & Dagher, A. (2008). Ghrelin modulates brain activity in areas that control appetitive behavior. Cell Metabolism, 7(5), 400-409. http://dx.doi.org/10.1016/j.cmet.2008.03.007
Mayer, J. (1955). Regulation of energy intake and the body weight: The glucostatic theory and the lipostatic hypothesis. Annals of the New York Academy of Sciences, 63(1), 15-43. http://dx.doi.org/10.1111/j.1749-6632.1955.tb36543.x
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Müller, T. D., Nogueiras, R., Andermann, M. L., Andrews, Z. B., Anker, S. D., Argente, J. (2015). Ghrelin. Institute of Neuroscience and Physiology, Molecular Metabolism, 4(6), 437-460. http://dx.doi.org/10.1016/j.molmet.2015.03.005
Saper, C. B., Chou, T. C., & Elmquist, J. K. (2002). The need to feed: Homeostatic and hedonic control of eating. Neuron, 36(2), 199-211. http://dx.doi.org/10.1016/S0896-6273(02)00969-8
Shufen, L. (2016). Leptin in normal physiology and leptin resistance. Science Bulletin 61(19), 1480-1488. http://dx.doi.org/10.1007/s11434-015-0951-4